Background: Long-term lithium use in psychiatric patients may lead to lithium associated hyperparathyroidism (LAH). Although anecdotal case reports have appeared, an evidence based algorithm for management of LAH is lacking. Methods: A comprehensive literature search was performed (1973-2010) using PubMed with keywords; “lithium” “hypercalcemia” “hyperparathyroidism” “sestamibi” “intra-operative parathyroid hormone (IOPTH) monitoring” “parathyroidectomy” and “medical management”. All English language publications addressing etiology and clinical management issues concerning LAH were critically analyzed. Results: Lithium associated hyperparathyroidism occurs in 4.3% - 6.3% of chronic lithium users compared to the general population which has an incidence of 0.5% - 1%. 194 cases of LAH have been reported which includes 10 patients (5%) treated medically and 170 patients (88%) who underwent parathyroidectomy. No details were available for 14 patients (7%). Among parathyroidectomy patients, 104 (59%) had adenomatous disease and 66 (39%) had multiglandular hyperplasia. Preoperative localization studies were utilized in only 22 patients (13%) and IOPTH monitoring was reported in only 3 studies (32 patients, 19%). Among surgical patients, bilateral neck exploration (BNE) was the most common approach performed in 162 patients (95%); focused neck exploration was utilized in only 8 patients (5%). Parathyroidectomy normalized LAH biochemical changes in nearly all patients (90% - 97%) in the early post-operative period, but recurrent hyperparathyroidism occurred in 8% - 42% of patients. Conclusion: LAH is an under appreciated and poorly understood endocrine disorder. LAH has a higher incidence of multiglandular disease and bilateral neck exploration is mandatory in majority for disease control. Nonsurgical approaches may be useful in select patients on short-term lithium therapy.
A. M. Nivoli, A. Murru and E. Vieta, “Lithium: Still a Cornerstone in the Long-Term Treatment in Bipolar Disorder?” Neuropsychobiology, Vol. 62, No. 1, 2010, pp. 27-35. doi:10.1159/000314307
W. Coryell, “Maintenance Treatment in Bipolar Disorder: A Reassessment of Lithium as the First Choice,” Bipolar Disorders, Vol. 11, No. 2, 2009, pp. 77-83. doi:10.1111/j.1399-5618.2009.00712.x
C. McHenry and K. Lee, “Lithium Therapy and Disorders of the Parathyroid Glands,” Endocrine Practice, Vol. 2, No. 2, 1996, pp. 103-109.
B. D. Saunders, E. F. Saunders and P. G. Gauger, “Lithium Therapy and Hyperparathyroidism: An Evidence-Based Assessment,” World Journal of Surgery, Vol. 33, No. 11, 2009, pp. 2314-2323. doi:10.1007/s00268-009-9942-4
S. S. Awad, J. Miskulin and N. Thompson, “Parathyroid Adenomas versus Four-Gland Hyperplasia as the Cause of Primary Hyperparathyroidism in Patients with Prolonged Lithium Therapy,” World Journal of Surgery, Vol. 27, No. 4, 2003, pp. 486-488. doi:10.1007/s00268-002-6824-4
N. Perera, L. Gluch and B. A. Crawford, “Misleading Parathyroid Sestamibi Scan in Lithium Users,” Internal Medicine Journal, Vol. 39, No. 8, 2009, pp. 556-557. doi:10.1111/j.1445-5994.2009.01972.x
J. I. Lew and C. C. Solorzano, “Surgical Management of Primary Hyperparatyroidism: State of the Art,” Surgical Clinics of North America, Vol. 89, No. 5, 2009, pp. 1205-1225. doi:10.1016/j.suc.2009.06.014
H. Bendz, I. Sjodin, G. Toss and K. Berglund, “Hyperparathyroidism and Long-Term Lithium Therapy: A Cross-Sectional Study and the Effect of Lithium Withdrawal,” Journal of Internal Medicine, Vol. 240, No. 6, 1996, pp. 357-365. doi:10.1046/j.1365-2796.1996.28864000.x
L. E. Mallette, K. Khouri, H. Zengotita, B. W. Hollis and S. Malini, “Lithium Treatment Increases Intact and Midregion Parathyroid Hormone and Parathyroid Volume,” The Journal of Clinical Endocrinology & Metabolism, Vol. 68, No. 3, 1989, pp. 654-660. doi:10.1210/jcem-68-3-654
P. E. Garfinkel, C. Ezrin and H. C. Stancer, “Hypothyroidism and Hyperparathyroidism Associated with Lithium,” Lancet, Vol. 2, 1973, pp. 331-332. doi:10.1016/S0140-6736(73)90846-5
C. Christiansen, P. C. Baastrup and I. Transbol, “Development of Primary Hyperparathyroidism during Lithium Therapy: Longitudinal Study,” Neuropsychobiology, Vol. 6, No. 5, 1980, pp. 280-283. doi:10.1159/000117770
A. Szalat, H. Mazeh and H. R. Freund, “Lithium-Associated Hyperparathyroidism: Report of Four Cases and Review of the Literature,” European Journal of Endocrinology, Vol. 160, No. 2, 2009, pp. 317-323. doi:10.1530/EJE-08-0620
C. R. McHenry, F. Racke, M. Meister, P. Warnaka, M. Sarasua, E. F. Nemeth, et al., “Lithium Effects on Dispersed Bovine Parathyroid Cell Grown in Tissue Culture,” Surgery, Vol. 110, No. 6, 1991, pp. 1061-1066.
J. Jarhult, S. Ander, B. Asking, S. Jansson, A. Meehan, A. Kristoffersson, et al., “Long-Term Results of Surgery for Lithium-Associated Hyperparathyroidism,” British Journal of Surgery, Vol. 97, No. 11, 2010, pp. 1680-1685.
W. Khairallah, A. Fawaz, E. M., Brown and G. El-Hajj Fuleihan, “Hypercalcemia and Diabetes Insipidus in a Patient Previously Treated with Lithium,” Nature Clinical Practice Nephrology, Vol. 3, No. 7, 2007, pp. 397-404. doi:10.1038/ncpneph0525
E. Carchman, J. Ogilvie, J. Holst, J. Yim and S. Carty, “Appropriate surgical Treatment of Lithium-Associated Hyperparathyroidism,” World Journal of Surgery, Vol. 32, No. 10, 2008, pp. 2195-2199. doi:10.1007/s00268-008-9616-7
H. Abdullah, R. Bliss, A. I. Guinea and L. Delbridge, “Pathology and Outcome of Surgical Treatment for Lithium-Associated Hyperparathyroidism,” British Journal of Surgery, Vol. 86, No. 1, 1999, pp. 91-93. doi:10.1046/j.1365-2168.1999.00977.x
J. C. Hundley, D. T. Woodrum, B. D. Saunders, G. M. Doherty and P. G. Gauger, “Revisiting Lithium-Associated Hyperparathyroidism in the Era of Intraoperative Parathyroid Hormone Monitoring,” Surgery, Vol. 138, No. 6, 2005, pp. 1027-1031. doi:10.1016/j.surg.2005.09.028
J. Nordenstrom, M. Elvius, M. Bagedahl-Strindlund, B. Zhao and O. Torring, “Biochemical Hyperparathyroidsm and Bone Mineral Status in Patients Treated Long-Term with Lithium,” Metabolism, Vol. 43, No. 12, 1994, 1563-1567. doi:10.1016/0026-0495(94)90017-5
J. Ananth and S. E. Dubin, “Lithium and Symptomatic Hyperparathyroidism,” Journal of the Royal Society of Medicine, Vol. 76, No. 12, 1983, pp. 1026-1029.
M. E. Wolf, M. Moffat, J. Mosnaim and S. Dempsey, “Lithium Therapy, Hypercalcemia, and Hyperparathyroidism,” American Journal of Therapeutics, Vol. 4, No. 9-10, 1997, pp. 323-325. doi:10.1097/00045391-199709000-00007
G. de Celis, M. Fiter, X. Latorre, and C. Llebaria, “Oxyphilic Parathyroid Adenoma and Lithium Therapy,” Lancet, Vol. 352, No. 9133, 1998, p. 1070. doi:10.1016/S0140-6736(05)60117-1
J. A. Sloand, M. A and M. A. Shelly, “Normalization of Lithium-Induced Hypercalcemia and Hyperparathyroidism with Cinacalcet Hydrochloride,” American Journal of Kidney Diseases, Vol. 48, No. 5, 2006, pp. 832-837. doi:10.1053/j.ajkd.2006.07.019
H. M. Khandwala and S. Van Uum, “Reversible hypercalcemia and Hyperparathyroidism Associatead with Lithiuim Therapy: Case Report and Review of Literature,” Endocrine Practice, Vol. 12, No. 1, 2006, pp. 54-58.
M. Rifai, J. K., Moles and D. P. Harrington, “Lithium-Induced Hypercalcemia and Parathyroid Dysfunction,” Psychosomatics, Vol. 42, No. 4, 2001, pp. 359-361. doi:10.1176/appi.psy.42.4.359
H. S. Duggal and I. Singh, “Lithium-Induced Hypercalcemia and Hyperparathyroidism Presenting with Delirium,” Prog Neuropsychopharmacol Biol Psychiatry, Vol. 32, No. 3, 2008, pp. 903-904. doi:10.1016/j.pnpbp.2007.12.014
M. M. Rizwan and N. D. Perrier, “Long-Term Lithium Therapy Leading to Hyperparathyroidism: A Case Report,” Perspect Psychiatr Care, Vol. 45. No. 1, 2009, pp. 62-65.
S. Carney and P. Jackson, “Acute Lithium Administration Impairs the Action of Parathyroid Hormone on Rat Renal Calcium Magnesium and Phosphate Transport,” Clinical and Experimental Pharmacology and Physiology, Vol. 25, No. 10, 1998, pp. 795-799. doi:10.1111/j.1440-1681.1998.tb02155.x
D. Riccardi and G. Gamba, “The Many Roles of the Calcium-Sensing Receptor in Health and Disease,” Archives of Medical Research, Vol. 30, No. 6, 1999, pp. 436-448. doi:10.1016/S0188-4409(99)00071-5
C. Livingstone and H. Rampes, “Lithium: A Review of Its Metabolic Adverse Effects,” Journal of Psychopharmacology, Vol. 20, No. 3, 2006, pp. 347-355. doi:10.1177/0269881105057515
F. H. Shen and D. J. Sherrard, “Lithium-Induced Hyperparathyroidism: An Alteration of the ‘Set Point’,” Annals of Internal Medicine, Vol. 96, No. 1, 1982, pp. 63-65.
E. M. Grandiean and J. M. Aubry, “Lithium: Updated Human Knowledge Using an Evidence-Based Approach: Part III: Clinical Safety,” CNS Drugs, Vol. 23, No. 5, 2009, pp. 397-418. doi:10.2165/00023210-200923050-00004
A. W. Saxe and G. Gibson, “Lithium Increases Tritiated Thymidine Uptake by Abnormal Human Parathyroid Tissue,” Surgery, Vol. 110, No. 6, 1991, pp. 1067-1076
P. S. Gregoor and G. M. de Jong, “Lithium Hypercalcemia, Hyperparathyroidism, and Cinacalcet,” Kidney Int, Vol. 71, No. 5, 2007, p. 470. doi:10.1038/sj.ki.5002065
L. A. Smith, V. Cornelius, A. Warnock, A. Bell and A. H. Young, “Effectiveness of Mood Stabilizers and Antipsychotics in the Maintenance Phase of Bipolar Disorder: A Systematic Review of Randomized Controlled Trials,” Bipolar Disorders, Vol. 9, No. 4, 2007, pp. 394-412. doi:10.1111/j.1399-5618.2007.00490.x
A. H. Young and J. M. Hammond, “Lithium in Mood Disorders: Increasing Evidence Base, declining Use?” The British Journal of Psychiatry, Vol. 191, 2007, pp. 474-476. doi:10.1192/bjp.bp.107.043133
M. A. Kouvaraki, M. Greer, S. Sharma, D. Beery, R. Armand, J. E. Lee, et al., “Indications for Operative Intervention in Patients with Asymptomatic Primary Hyperparathyroidism: Practice Patterns of Endocrine Surgery,” Surgery, Vol. 139, No. 4, 2006, pp. 527-534. doi:10.1016/j.surg.2005.09.006